MicroRNA (miR)-21 has been identified as a novel biomarker of hepatocellular carcinoma (HCC). However, the prognostic value of miR-21 expression in HCC remains controversial. The aim of the present study was to investigate the value of high expression of miR-21 in predicting the prognosis of HCC. Following a search through the PubMed, Science Citation Index, EMBASE and CNKI databases, a total of 9 studies investigating the expression of miR-21 in HCC and the association between high expression of miR-21 and prognosis of HCC were identified. It was observed that high expression of miR-21 was not associated with poor overall survival of all patients with HCC (P=0.52). However, high expression of miR-21 was found to be correlated with poor prognosis of HCC patients undergoing curative resection (hazard ratio = 2.36; P<0.01). It was also demonstrated that high expression of miR-21 was correlated with tumor size >5 cm [odds ratio (OR)=1.53; P=0.04], venous invasion (OR=4.86; P=0.01), TNM stage (OR=3.44; P<0.01) and liver cirrhosis (OR=2.12; P=0.03). It was concluded that miR-21 cannot be considered as a factor complementary to α-fetoprotein, microvascular invasion and advanced tumor stage in predicting the prognosis of all HCC patients. Higher expression of miR-21 may be a promising biomarker associated with certain clinicopathological characteristics of HCC, such as tumor size, venous invasion, TNM stage and liver cirrhosis.